Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence

Detalhes bibliográficos
Autor(a) principal: Weinberger, Martin
Data de Publicação: 2010
Outros Autores: Mesquita, Ana Maria Macedo, Carroll, Timothy, Marks, Laura, Hui Yang, Zhaojie Zhang, Ludovico, Paula, Burhans, William C
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/29582
Resumo: Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H2O2, which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes.
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spelling Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescenceOxidative stressReplication stressLifespanCaloric restrictionHydrogen peroxideScience & TechnologyInhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H2O2, which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes.This research was supported by a National Cancer Institute Cancer Center Support Grant (P30 CA016056) to Roswell Park Cancer Institute and a fellowship to A. M. from Fundacao para a Ciencia e Tecnologia (SFRH/BD/32464/2006). We are grateful to Molly Burhans for preparation of Figure 6.Impact JournalsUniversidade do MinhoWeinberger, MartinMesquita, Ana Maria MacedoCarroll, TimothyMarks, LauraHui YangZhaojie ZhangLudovico, PaulaBurhans, William C2010-102010-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/29582eng1945-458910.18632/aging.10021521076178http://www.impactaging.com/info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:31:38Zoai:repositorium.sdum.uminho.pt:1822/29582Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:26:53.505755Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
spellingShingle Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
Weinberger, Martin
Oxidative stress
Replication stress
Lifespan
Caloric restriction
Hydrogen peroxide
Science & Technology
title_short Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_full Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_fullStr Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_full_unstemmed Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_sort Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
author Weinberger, Martin
author_facet Weinberger, Martin
Mesquita, Ana Maria Macedo
Carroll, Timothy
Marks, Laura
Hui Yang
Zhaojie Zhang
Ludovico, Paula
Burhans, William C
author_role author
author2 Mesquita, Ana Maria Macedo
Carroll, Timothy
Marks, Laura
Hui Yang
Zhaojie Zhang
Ludovico, Paula
Burhans, William C
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Weinberger, Martin
Mesquita, Ana Maria Macedo
Carroll, Timothy
Marks, Laura
Hui Yang
Zhaojie Zhang
Ludovico, Paula
Burhans, William C
dc.subject.por.fl_str_mv Oxidative stress
Replication stress
Lifespan
Caloric restriction
Hydrogen peroxide
Science & Technology
topic Oxidative stress
Replication stress
Lifespan
Caloric restriction
Hydrogen peroxide
Science & Technology
description Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H2O2, which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
2010-10-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/29582
url http://hdl.handle.net/1822/29582
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1945-4589
10.18632/aging.100215
21076178
http://www.impactaging.com/
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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